Topical Clobetasol for the Treatment of Toxic Epidermal Necrolysis

Phase 1

Withdrawn

• Conditions: Toxic Epidermal Necrolysis
• Interventions: Drug: Clobetasol 0.05% ointment; Drug: Placebo

• Registration Number: NCT02319616
• Lead Sponsor: University of California, Davis

Brief Summary

The primary objectives of this study are to investigate the efficacy and safety of topical steroid ointment (clobetasol 0.05%) for the treatment of the cutaneous manifestations of toxic epidermal necrolysis (TEN).

Detailed Description

The experimental focus of this trial is thus to evaluate the safety and clinical outcomes of topical steroid (clobetasol 0.05% ointment) for treatment of the cutaneous manifestations of toxic epidermal necrolysis (TEN).

The design of the study is a randomized, placebo-controlled, double-blind split-body Phase II clinical trial in which clobetasol 0.05% or placebo ointment will be topically applied to opposite arms for a period of fourteen days. The primary endpoints of the study are to determine the time to cessation of skin detachment in both groups as well as the safety of topical clobetasol to treat the cutaneous manifestations of TEN. Secondary outcome measures will evaluate efficacy by comparing the time to re-epithelialization and the percentage of affected skin between the clobetasol and placebo arms at various time points.

An additional aim of the study is to characterize the genes expressed during the TEN disease state and any changes in gene expression following treatment with topical steroids, particularly those genes involved in the regulation of programmed cell death (apoptosis). This will be accomplished though molecular analysis of skin biopsy specimens obtained after treatment with clobetasol and placebo ointments. The specific hypothesis being tested is that two weeks of topical clobetasol will promote epidermal keratinocyte survival through suppression of TNF signaling, decreased granulysin expression and inhibition of other pro-apoptotic pathways resulting in shorter disease duration and decreased time to re-epithelialization.

IRB number: 642415-5

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2014-12-15
• Study First Submitted QC: 2014-12-17
• Study First Posted: 2014-12-18
• Study Start: 2016-11
• Primary Completion: 2019-02-06
• Study Completion: 2019-02-06
• Status Verified: 2019-08
• Last Update Submitted: 2019-08-07
• Last Update Posted: 2019-08-09

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Characteristic histological findings on diagnostic biopsy
• Clinical diagnosis verified by two independent physicians
• Greater than 10% affected body surface area (BSA)
• Ability to start treatment within seven days or less from the onset of erosions
• Actively worsening disease (enlarging area of involvement or new erosions occurring over the last 24 hours)
• Patient Body Surface Area (BSA) > 1.0 m2
• Reproductive age female patients must have a negative pregnancy test prior to enrollment

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Exclusion Criteria

• Patients will be excluded if they are < 7 or > 85 years of age.

• Patients who have documented:

  • Uncontrolled infection (e.g. documented bacteremia)
  • Malignancy
  • Known prior immunodeficiency
  • Pregnancy
  • Concurrent use of systemic corticosteroids in the burn center greater than or equal to 0.5 mg/kg/day of prednisone or equivalent dose of similar medication.
  • Greater than 70% eroded skin
  • SCORETEN score >3 on hospital admission

• Patients will also be excluded if they have: active hepatitis and/or an ALT or AST greater than four times the normal limits, or renal insufficiency with an estimated GFR<50 mL/min/1.73m2.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Clobetasol 0.05% ointment	Clobetasol 0.05% ointment	All patients will have one arm assigned to receive the experimental treatment (topical clobetasol 0.05% ointment) applied daily for a period of fourteen days.
Placebo	Placebo	All patients will have one arm assigned to receive the placebo treatment (topical petrolatum ointment) applied daily for a period of fourteen days.

Primary Outcome Measures

Name	Time	Method
Time to Cessation of Skin Detachment	14 days	The time until cessation of skin detachment (measured in days) will be determined though daily skin examinations and compared between the clobetasol and placebo-treated skin of patients with toxic epidermal necrolysis.
Safety (numeric cellulitis score)	14 days	Local infection (cellulitis) is a potential complication of treatment with topical steroid ointment. A primary outcome measure of the study will be to determine if any difference in local infection rate exists between between control and clobetasol-treated skin in patients with toxic epidermal necrolysis, determined by daily assessments and assignment of a numeric cellulitis score.

Secondary Outcome Measures

Name	Time	Method
Time to 90% re-epithelialization	14 days	The time to 90% re-epithelialization will be determined by daily skin examinations and recorded in days to determine if a significant difference exists between control and clobetasol treated skin.
Percent Affected Surface Area	14 days	Percent affected surface area will be measured with daily skin examinations and compared between the placebo and steroid treated skin in patients with TEN
Percent Affected Surface Area Detached Skin	14 days	The percent body surface area affected by detached skin will be monitored through daily skin examinations and compared between the clobetasol and placebo treated skin in patients with toxic epidermal necrolysis.

Trial Locations

Locations (1)

University of California, Davis Department of Dermatology; 🇺🇸 Sacramento, California, United States